Difference between revisions of "CNS melanoma"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
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{| class="wikitable" style="text-align:center; width:100%;"
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{{#lst:Editorial board transclusions|cns-mel}}
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! colspan="4" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Section editors'''
 
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| style="background-color:#F0F0F0; width:15%" |[[File:SeemaNagpal.jpg|frameless|upright=0.3|center]]
 
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| style="width:35%" |<big>[[User:Seemanagpal|Seema Nagpal, MD]]<br>Stanford University<br>Palo Alto, CA</big>
 
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| style="background-color:#F0F0F0; width:15%" |[[File:Bethbuchbinder.jpg|frameless|upright=0.3|center]]
 
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| style="width:35%" |<big>[[User:Bethbuchbinder|Elizabeth Buchbinder, MD]]<br>Dana-Farber Cancer Institute<br>Boston, MA</big><br>[https://www.linkedin.com/in/beth-buchbinder-2a9b994/ LinkedIn]
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
|}
 
|}
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<big>'''Note: these are CNS-specific regimens, please see the [[Melanoma|main melanoma page]] for other regimens.'''</big>
+
'''Note: these are CNS-specific regimens, please see the [[Melanoma|main melanoma page]] for other regimens.'''
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 
==EANO/ESMO==
 
==EANO/ESMO==
−
*'''2017:''' Le Rhun et al. [https://www.esmo.org/Guidelines/Neuro-Oncology/EANO-ESMO-Leptomeningeal-Metastasis-Clinical-Practice-Guidelines EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours]
+
*'''2017:''' Le Rhun et al. [https://www.esmo.org/Guidelines/Neuro-Oncology/EANO-ESMO-Leptomeningeal-Metastasis-Clinical-Practice-Guidelines EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours] [https://www.ncbi.nlm.nih.gov/pubmed/28881917 PubMed]
−
==[https://www.nccn.org/ NCCN]==
+
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf NCCN Guidelines - Central Nervous System Cancers]
+
==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1492 NCCN Guidelines - Cutaneous Melanoma] and [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425 NCCN Guidelines - Central Nervous System Cancers].''
 +
 
 
=All lines of therapy=
 
=All lines of therapy=
 
==Dabrafenib monotherapy {{#subobject:8f3562|Regimen=1}}==
 
==Dabrafenib monotherapy {{#subobject:8f3562|Regimen=1}}==
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</div></div>
 
</div></div>
 
===References===
 
===References===
−
#'''BREAK-MB:''' Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin AM, Guckert M, Goodman V, Streit M, Kirkwood JM, Schadendorf D. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Nov;13(11):1087-95. Epub 2012 Oct 8. [https://doi.org/10.1016/S1470-2045(12)70431-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23051966/ PubMed] NCT01266967
+
#'''BREAK-MB:''' Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin AM, Guckert M, Goodman V, Streit M, Kirkwood JM, Schadendorf D. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Nov;13(11):1087-95. Epub 2012 Oct 8. [https://doi.org/10.1016/S1470-2045(12)70431-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23051966/ PubMed] [https://clinicaltrials.gov/study/NCT01266967 NCT01266967]
 
==Dabrafenib & Trametinib {{#subobject:7d3694|Regimen=1}}==
 
==Dabrafenib & Trametinib {{#subobject:7d3694|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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</div></div>
 
</div></div>
 
===References===
 
===References===
−
#'''COMBI-MB:''' Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Márquez-Rodas I, Del Vecchio M, Lebbé C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. Dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):863-873. Epub 2017 Jun 4. [https://doi.org/10.1016/S1470-2045(17)30429-1 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5991615/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28592387/ PubMed] NCT02039947
+
#'''COMBI-MB:''' Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Márquez-Rodas I, Del Vecchio M, Lebbé C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. Dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):863-873. Epub 2017 Jun 4. [https://doi.org/10.1016/S1470-2045(17)30429-1 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5991615/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28592387/ PubMed] [https://clinicaltrials.gov/study/NCT02039947 NCT02039947]
  
 
==Fotemustine monotherapy {{#subobject:28162f|Regimen=1}}==
 
==Fotemustine monotherapy {{#subobject:28162f|Regimen=1}}==
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|1991-1997
 
|1991-1997
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Fotemustine_.26_WBRT_99|Fotemustine & WBRT]]
+
|[[#Fotemustine_.26_WBRT_999|Fotemustine & WBRT]]
 
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
|-
 
|-
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|rowspan=2|2013-2018
 
|rowspan=2|2013-2018
 
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
−
|1. [[#Fotemustine_.26_Ipilimumab_99|Fotemustine & Ipilimumab]]
+
|1. [[#Fotemustine_.26_Ipilimumab_999|Fotemustine & Ipilimumab]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
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===References===
 
===References===
 
# Mornex F, Thomas L, Mohr P, Hauschild A, Delaunay MM, Lesimple T, Tilgen W, Bui BN, Guillot B, Ulrich J, Bourdin S, Mousseau M, Cupissol D, Bonneterre ME, De Gislain C, Bensadoun RJ, Clavel M. A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma. Melanoma Res. 2003 Feb;13(1):97-103. [https://doi.org/10.1097/00008390-200302000-00016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12569292/ PubMed]
 
# Mornex F, Thomas L, Mohr P, Hauschild A, Delaunay MM, Lesimple T, Tilgen W, Bui BN, Guillot B, Ulrich J, Bourdin S, Mousseau M, Cupissol D, Bonneterre ME, De Gislain C, Bensadoun RJ, Clavel M. A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma. Melanoma Res. 2003 Feb;13(1):97-103. [https://doi.org/10.1097/00008390-200302000-00016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12569292/ PubMed]
−
#'''NIBIT-M2:''' Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, Ferrucci PF, Guida M, Quaglino P, Guidoboni M, Marchetti P, Cutaia O, Amato G, Covre A, Camerini R, Calabrò L, Valente M, Giannarelli D, Mandalà M, Maio M. Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021 Sep 1;27(17):4737-4745. Epub 2021 Jun 10. [https://doi.org/10.1158/1078-0432.ccr-21-1046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34112708/ PubMed] NCT02460068
+
#'''NIBIT-M2:''' Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, Ferrucci PF, Guida M, Quaglino P, Guidoboni M, Marchetti P, Cutaia O, Amato G, Covre A, Camerini R, Calabrò L, Valente M, Giannarelli D, Mandalà M, Maio M. Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021 Sep 1;27(17):4737-4745. Epub 2021 Jun 10. [https://doi.org/10.1158/1078-0432.ccr-21-1046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34112708/ PubMed] [https://clinicaltrials.gov/study/NCT02460068 NCT02460068]
 
==Ipilimumab & Nivolumab {{#subobject:28103f|Regimen=1}}==
 
==Ipilimumab & Nivolumab {{#subobject:28103f|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
|1. [[#Fotemustine_monotherapy|Fotemustine]]
 
|1. [[#Fotemustine_monotherapy|Fotemustine]]
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 29.2 vs 8.5 mo<br>(HR 0.44, 95% CI 0.22-0.87)
+
| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 29.2 vs 8.5 mo<br>(HR 0.44, 95% CI 0.22-0.87)
 
|-
 
|-
−
|2. [[#Fotemustine_.26_Ipilimumab_99|Fotemustine & Ipilimumab]]
+
|2. [[#Fotemustine_.26_Ipilimumab_999|Fotemustine & Ipilimumab]]
 
| style="background-color:#d3d3d3" |Not reported
 
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
Line 144: Line 139:
 
|2014-2017
 
|2014-2017
 
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
−
|[[#Nivolumab_monotherapy_88|Nivolumab]]
+
|[[#Nivolumab_monotherapy_999|Nivolumab]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of intracranial response from week 12
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of intracranial response from week 12
 
|-
 
|-
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</div></div>
 
</div></div>
 
===References===
 
===References===
−
#'''ANZMTG 01.14:''' Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, Menzies AM, McArthur GA. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 Mar 27. [https://doi.org/10.1016/S1470-2045(18)30139-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29602646/ PubMed] NCT02374242
+
#'''ANZMTG 01.14:''' Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, Menzies AM, McArthur GA. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 May;19(5):672-681. Epub 2018 Mar 27. [https://doi.org/10.1016/S1470-2045(18)30139-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29602646/ PubMed] [https://clinicaltrials.gov/study/NCT02374242 NCT02374242]
−
#'''CheckMate 204:''' Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA, Atkins MB, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Thomas RP, Tarhini A, Pavlick AC, Jiang J, Avila A, Demelo S, Margolin K. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018 Aug 23;379(8):722-730. [https://doi.org/10.1056/nejmoa1805453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8011001/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30134131/ PubMed] NCT02320058
+
#'''CheckMate 204:''' Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA, Atkins MB, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Thomas RP, Tarhini A, Pavlick AC, Jiang J, Avila A, Demelo S, Margolin K. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018 Aug 23;379(8):722-730. [https://doi.org/10.1056/nejmoa1805453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8011001/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30134131/ PubMed] [https://clinicaltrials.gov/study/NCT02320058 NCT02320058]
 
##'''Update:''' Tawbi HA, Forsyth PA, Hodi FS, Lao CD, Moschos SJ, Hamid O, Atkins MB, Lewis K, Thomas RP, Glaspy JA, Jang S, Algazi AP, Khushalani NI, Postow MA, Pavlick AC, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Tarhini AA, Sumbul A, Rizzo JI, Margolin KA. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro Oncol. 2021 Nov 2;23(11):1961-1973. [https://doi.org/10.1093/neuonc/noab094 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8563325/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33880555/ PubMed]
 
##'''Update:''' Tawbi HA, Forsyth PA, Hodi FS, Lao CD, Moschos SJ, Hamid O, Atkins MB, Lewis K, Thomas RP, Glaspy JA, Jang S, Algazi AP, Khushalani NI, Postow MA, Pavlick AC, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Tarhini AA, Sumbul A, Rizzo JI, Margolin KA. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro Oncol. 2021 Nov 2;23(11):1961-1973. [https://doi.org/10.1093/neuonc/noab094 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8563325/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33880555/ PubMed]
−
#'''NIBIT-M2:''' Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, Ferrucci PF, Guida M, Quaglino P, Guidoboni M, Marchetti P, Cutaia O, Amato G, Covre A, Camerini R, Calabrò L, Valente M, Giannarelli D, Mandalà M, Maio M. Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021 Sep 1;27(17):4737-4745. Epub 2021 Jun 10. [https://doi.org/10.1158/1078-0432.ccr-21-1046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34112708/ PubMed] NCT02460068
+
#'''NIBIT-M2:''' Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, Ferrucci PF, Guida M, Quaglino P, Guidoboni M, Marchetti P, Cutaia O, Amato G, Covre A, Camerini R, Calabrò L, Valente M, Giannarelli D, Mandalà M, Maio M. Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021 Sep 1;27(17):4737-4745. Epub 2021 Jun 10. [https://doi.org/10.1158/1078-0432.ccr-21-1046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34112708/ PubMed] [https://clinicaltrials.gov/study/NCT02460068 NCT02460068]
 +
 
 
==Vemurafenib monotherapy {{#subobject:28825f|Regimen=1}}==
 
==Vemurafenib monotherapy {{#subobject:28825f|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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</div></div>
 
</div></div>
 
===References===
 
===References===
−
#'''MO25743:''' McArthur GA, Maio M, Arance A, Nathan P, Blank C, Avril MF, Garbe C, Hauschild A, Schadendorf D, Hamid O, Fluck M, Thebeau M, Schachter J, Kefford R, Chamberlain M, Makrutzki M, Robson S, Gonzalez R, Margolin K. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol. 2017 Mar 1;28(3):634-641. [https://doi.org/10.1093/annonc/mdw641 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27993793/ PubMed] NCT01378975
+
#'''MO25743:''' McArthur GA, Maio M, Arance A, Nathan P, Blank C, Avril MF, Garbe C, Hauschild A, Schadendorf D, Hamid O, Fluck M, Thebeau M, Schachter J, Kefford R, Chamberlain M, Makrutzki M, Robson S, Gonzalez R, Margolin K. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol. 2017 Mar 1;28(3):634-641. [https://doi.org/10.1093/annonc/mdw641 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27993793/ PubMed] [https://clinicaltrials.gov/study/NCT01378975 NCT01378975]
 
[[Category:CNS melanoma regimens]]
 
[[Category:CNS melanoma regimens]]
 
[[Category:Site-specific pages]]
 
[[Category:Site-specific pages]]
 
[[Category:CNS cancers]]
 
[[Category:CNS cancers]]

Latest revision as of 00:25, 4 July 2024

Back to Top

Section editor Section editor
SeemaNagpal.jpg
 Seema Nagpal, MD
Stanford University
Palo Alto, CA, USA
LinkedIn
Bethbuchbinder.jpg
 Elizabeth Buchbinder, MD
Dana-Farber Cancer Institute
Boston, MA, USA
LinkedIn
5 regimens on this page
5 variants on this page

Note: these are CNS-specific regimens, please see the main melanoma page for other regimens.


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

EANO/ESMO

NCCN

All lines of therapy

Dabrafenib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Long et al. 2012 (BREAK-MB) 2011 Phase 2 (RT) ORR: 31-39%

Biomarker eligibility criteria

  • BRAF V600 mutant
  • Study Inclusion criteria: Val600Glu or Val600Lys

Targeted therapy

Continued indefinitely

References

  1. BREAK-MB: Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin AM, Guckert M, Goodman V, Streit M, Kirkwood JM, Schadendorf D. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Nov;13(11):1087-95. Epub 2012 Oct 8. link to original article contains dosing details in manuscript PubMed NCT01266967

Dabrafenib & Trametinib

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Davies et al. 2017 (COMBI-MB) 2014-2016 Phase 2 (RT) ORR: 44-59%

Biomarker eligibility criteria

  • BRAF V600 mutant
  • Clinical Trial Inclusion: BRAF V600 E/K/D/R

Targeted therapy

Continued indefinitely

References

  1. COMBI-MB: Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Márquez-Rodas I, Del Vecchio M, Lebbé C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. Dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):863-873. Epub 2017 Jun 4. link to original article contains dosing details in abstract link to PMC article PubMed NCT02039947

Fotemustine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Mornex et al. 2003 1991-1997 Phase 3 (C) Fotemustine & WBRT Did not meet endpoint of OS
Di Giacomo et al. 2021 (NIBIT-M2) 2013-2018 Phase 3 (C) 1. Fotemustine & Ipilimumab Did not meet primary endpoint of OS
2. Ipilimumab & Nivolumab Inferior OS

Chemotherapy

References

  1. Mornex F, Thomas L, Mohr P, Hauschild A, Delaunay MM, Lesimple T, Tilgen W, Bui BN, Guillot B, Ulrich J, Bourdin S, Mousseau M, Cupissol D, Bonneterre ME, De Gislain C, Bensadoun RJ, Clavel M. A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma. Melanoma Res. 2003 Feb;13(1):97-103. link to original article PubMed
  2. NIBIT-M2: Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, Ferrucci PF, Guida M, Quaglino P, Guidoboni M, Marchetti P, Cutaia O, Amato G, Covre A, Camerini R, Calabrò L, Valente M, Giannarelli D, Mandalà M, Maio M. Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021 Sep 1;27(17):4737-4745. Epub 2021 Jun 10. link to original article PubMed NCT02460068

Ipilimumab & Nivolumab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Di Giacomo et al. 2021 (NIBIT-M2) 2013-2018 Phase 3 (E-esc) 1. Fotemustine Superior OS (primary endpoint)
Median OS: 29.2 vs 8.5 mo
(HR 0.44, 95% CI 0.22-0.87)
2. Fotemustine & Ipilimumab Not reported
Long et al. 2018 (ANZMTG 01.14) 2014-2017 Randomized Phase 2 (E-esc) Nivolumab Did not meet primary endpoint of intracranial response from week 12
Tawbi et al. 2018 (CheckMate 204) 2015-2017 Phase 2

Immunotherapy

  • Ipilimumab (Yervoy) as follows:
    • Cycles 1 to 4: 3 mg/kg IV once on day 1
  • Nivolumab (Opdivo) as follows:
    • Cycles 1 to 4: 1 mg/kg IV once on day 1
    • Cycle 5 onwards: 3 mg/kg IV over 60 minutes once on day 1

21-day cycle for 4 cycles, then 14-day cycles

References

  1. ANZMTG 01.14: Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, Menzies AM, McArthur GA. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 May;19(5):672-681. Epub 2018 Mar 27. link to original article contains dosing details in manuscript PubMed NCT02374242
  2. CheckMate 204: Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA, Atkins MB, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Thomas RP, Tarhini A, Pavlick AC, Jiang J, Avila A, Demelo S, Margolin K. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018 Aug 23;379(8):722-730. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02320058
    1. Update: Tawbi HA, Forsyth PA, Hodi FS, Lao CD, Moschos SJ, Hamid O, Atkins MB, Lewis K, Thomas RP, Glaspy JA, Jang S, Algazi AP, Khushalani NI, Postow MA, Pavlick AC, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Tarhini AA, Sumbul A, Rizzo JI, Margolin KA. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro Oncol. 2021 Nov 2;23(11):1961-1973. link to original article link to PMC article PubMed
  3. NIBIT-M2: Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, Ferrucci PF, Guida M, Quaglino P, Guidoboni M, Marchetti P, Cutaia O, Amato G, Covre A, Camerini R, Calabrò L, Valente M, Giannarelli D, Mandalà M, Maio M. Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021 Sep 1;27(17):4737-4745. Epub 2021 Jun 10. link to original article PubMed NCT02460068

Vemurafenib monotherapy

Regimen

Study Dates of enrollment Evidence
McArthur et al. 2017 (MO25743) 2011-2013 Phase 2 (RT)

Biomarker eligibility criteria

Targeted therapy

References

  1. MO25743: McArthur GA, Maio M, Arance A, Nathan P, Blank C, Avril MF, Garbe C, Hauschild A, Schadendorf D, Hamid O, Fluck M, Thebeau M, Schachter J, Kefford R, Chamberlain M, Makrutzki M, Robson S, Gonzalez R, Margolin K. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol. 2017 Mar 1;28(3):634-641. link to original article PubMed NCT01378975
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